The overall objective continues to be the elucidation of the molecular mechanisms of actions of mammalian hormones whose physiological effects are mediated by or related to cyclic nucleotides, and studies of aberrancies in these mechanisms which result in disease. This renewal application includes studies on: hormone receptors in states involving abnormal sensitivity to hormones and other physiological effectors; identification, isolation and characterization of hepatic receptors for glucagon, secretin, vasoactive intestinal polypeptide, insulin, somatomedins and NSILA-s; prostaglandin receptors in the cardiovascular system; dopamine receptors in brain synaptic membranes; induction and ontogeny of polypeptide hormone receptors, adenylate cyclase, cyclic nucleotide phosphodiesterase, and plasma membrane components; pancreatic receptors involved in the biosynthesis of insulin and glucagon; mechanism of the "permissive" action of adrenal glucocorticoids; and isolation of adrenal cortical ACTH receptor.